Seasonal Affective Disorder

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This article refers to the International Classification of Diseases 10th edition (ICD-10) which is the official classification system for mental health professionals working in NHS clinical practice. The literature occasionally refers to the Diagnostic and Statistical Manual of Mental Disorders (DSM) classification system which - whilst used in clinical practice in the USA - is primarily used for research purposes elsewhere.

Low mood during winter months has been noted as far back as 1845; however, it was not formally recognised as a disorder until the 1980s.

Seasonal affective disorder (SAD) is now classified as a variant of depression, characterised by depressive episodes that recur annually at the same time each year, usually during the winter months. It can be very disabling for patients, some of whom may require hospitalisation for SAD at some point.

SAD patients spend over 40% of the year struggling with substantial depressive symptoms during most years, beginning in young adulthood.

Light and darkness are thought to affect mood and behaviour via the complex interaction between circadian rhythms and the biological clocks which control them.

Circadian rhythms are innate physiological, mental and behavioural changes which follow a roughly 24- to 25-hour cycle. Biological clocks are groups of interacting molecules in cells throughout the body. A master biological clock is located in the supra-chiasmic nucleus (SCN) which sits within the hypothalamus. This co-ordinates all the body clocks so that they are synchronised.

The master clock in the SCN is affected by light and darkness via the retino-hypothalamic tract. The retino-hypothalamic tract is a neurological pathway connecting the retinal ganglion cells (RGCs) of the retinae to the SCN in the hypothalamus. This connects with the pineal gland via the superior cervical ganglion (SCG).

RGCs → melanopsin → SCN → SCG → pineal gland → supression ofmelatonin

Sunlight (or light at 480 nm) stimulates the RGCs to produce the photoreceptor melanopsin. Melanopsin 'signals' daytime to the SCN which in turn induces the pineal gland to suppress melatonin production.

Melatonin is produced by the pineal gland. Its primary function is to signal day length to the SCN, acting as a cue for innate night-time behaviour. Via the activation of melatonin receptors, it affects sleep propensity and the sleep/wake rhythm, circadian rhythms; it induces heat loss, reduces arousal and delays cortisone production. Melatonin is synthesised from serotonin, which is in turn synthesised from L-tryptophan. Large increases in melatonin production at night are due to a concomitant increase in the activity of the penultimate enzyme in melatonin synthesis, arylalkylamine N-acetyltransferase (serotonin N-acetyltransferase, AANAT). Serotonin levels have a major role in mood modulation.

Despite ardent research, the cause of SAD is not yet fully understood. One prevailing theory is that patients with SAD are phase-delayed[7]. This suggests that most patients with SAD become depressed in the winter, at least in part because of a phase delay in circadian rhythms relative to the sleep/wake cycle. The cause of this 'phase delay' and why it has such a pronounced effect on mood and behaviour, is likely to be multifactorial, involving abnormalities at various levels along the retino-hypothalamic tract, its links with the pineal gland, and the metabolism of melatonin and serotonin. Familial studies suggest a higher incidence of SAD among first-degree relatives, with genetic factors accounting for between 29-69% of variance in seasonal mood symptoms[8]. This suggests that genetic aberrations may underlie the various abnormalities which cause SAD symptoms.

Melatonin secretion occurs later in the night and for longer periods during the early morning compared to healthy individuals.

Sensitivity to light and melanopsin in SAD patients

Studies have shown that the retinal sensitivity to light is decreased in SAD patients compared to controls and that this reduced sensitivity is more frequent among those with a mutated variant of the melanopsin gene[9].

Preliminary investigations have found that individuals with a mutated variant of the melanopsin gene (TT) were 5.6 times more likely to have SAD than those without this variant[8].

Sleep onset among those with the TT genotype was later in the day when individuals were assessed on longer days and earlier in the day on shorter days, whereas individuals in the other genotype groups (ie CC and CT) did not show this interaction effect[10].

It is well established that serotonin has a major role in suppressing various aspects of feeding behaviour. SAD patients report distinct subjective responses to high-carbohydrate meals, which can enhance serotonin turnover via increased tryptophan uptake into the brain.

Serotonin levels in human post-mortem samples are found to be at minimum levels during the winter months.

Depletion of L-tryptophan, which is a precursor of serotonin, is associated with a relapse of depressive symptoms in patients who are in remission due to light therapy.

Although treatment with melatonin itself is not helpful for people with SAD, the novel drug agomelatine, which acts as a melatonin receptor agonist - but also as a 5HT2C antagonist (and so increases serotonin availability at the synapse) - has been found to have good results in treating SAD.

Exercise, which activates the serotoninergic system potentiates light-induced delays of circadian rhythms.

Classification and seasonal affective disorder variants

SAD with autumn- or winter-onset depression, with symptoms remitting or hypomanic or manic symptoms during the spring or summer, is the most common.

Sub-syndromal SAD is characterised by seasonal mood disruptions with milder functional impairments. Symptom changes may not be as severe. Patients may not meet Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Text Revision (DSM-IV-TR) or International Classification of Diseases Tenth Revision (ICD-10) criteria for a clinical mood disorder. However, the mood disruption and impairments may still be significant.

SAD with summer onset of depressive symptoms, with remission or hypomanic or manic symptoms during the winter months (less common than autumn- or winter-onset depression).

Presentation

Patients may develop the following symptoms in a step-wise fashion, beginning in September and culminating with depression and anxiety in December. SAD symptoms persist until springtime in April.

Differential diagnosis

Bipolar I and ll disorders (all patients with autumn- or winter-onset depression should be screened for spring or summer hypomania or mania symptoms. An estimated 20% of people with SAD may present with a bipolar disorder).

Dysthymic disorder.

Cyclothymic disorder.

Premenstrual dysphoric disorder (associated with bloating and breast tenderness with onset during the later part of the luteal phase of the menstrual cycle and remission of symptoms during the follicular phase).

Many of these disorders do not have a seasonal pattern. The seasonality of symptoms may be determined by asking the patient to record symptoms in a diary or using the seasonal pattern assessment questionnaire (SPAQ)[13].

Investigations

TFTs and urine and blood tests for illicit substances and alcohol will help to rule out some of the above conditions.

Diagnosis

SAD is categorised as a form of depressive disorder in the DSM-IV. The gold standard for diagnosis is a structured interview to determine whether patients fulfil the DSM-IV criteria. The SIGH-SAD clinical assessment tool is commonly used .

The most current National Institute for Health and Care Excellence (NICE) guidelines for depression state that depression in SAD patients should be managed in the same way as non-seasonal depression[17].

Cognitive behavioural therapy (CBT), light therapy and prescribed medications have all been found to help to induce remission of SAD symptoms during winter months. In patients with SAD, or with symptoms that are highly suspicious of it, it is important not to wait until they are showing signs of depression but to start non-drug treatment while they have early symptoms such as lethargy and carbohydrate cravings around September.

Light therapy, or phototherapy, has been associated with a reduction in depression fatigue, sleepiness and health-related quality of life.

It may be carried out using various devices such as a light box, LED screen and a light room; however, the light box is the most commonly used.

Light therapy with a light box that meets evidence-based guidelines from a reputable vendor, is recommended for first-line treatment of SAD. Self-reported reductions in depression scores have been demonstrated after one hour of light therapy exposure[19].

General instructions for light therapy

Sit for 30-60 minutes daily in an area with bright light. The light is much stronger than regular light sources, of the order of 2,500-10,000 lux (the greater the lux, the less time of exposure required).

Light therapy helps approximately two thirds of patients .

Although randomised trials are difficult to perform, attempts at comparisons of light therapy show that light therapy is as effective as drug therapy .

Light therapy can take several weeks to produce any effect; if it takes longer than six weeks, extra help should be sought. However, it is not available on the NHS, although some hospitals may have facilities available on site.

Common side-effects include headache, irritability and fatigue.

Dawn simulators are also available.

Despite all of these, more lux is available from natural sunlight.

Relative contra-indications for light therapy

Retinal disease.

Macular degeneration.

Current use of photosensitising medicines (such as some antihypertensives, antibiotics and oncology drugs).

Compliance with light therapy is difficult and relapses occur rapidly if treatment is discontinued.

There are little good-quality data supporting the use of antidepressants (citalopram, paroxetine, and escitalopram and duloxetine) for the treatment of SAD.

Up to 27% of participants treated with second-generation antidepressants for SAD withdrew from the studies early due to adverse effects.

Fluoxetine has been found to have a non-statistically significant improvement compared with placebo; it has been found to be at least as effective as light therapy. Light therapy, however, has fewer side-effects.

Combined light therapy and antidepressant therapy can be initiated in many SAD patients. More severe and functionally impairing depressive symptoms may warrant combined treatments. Depressive symptoms that do not fully remit during the spring or summer months may also warrant combined treatments.

Despite its efficacy, light therapy is associated with poor compliance. A small trial has found CBT to be associated with significantly lower interviewer- and patient-related depression severity at one year, as compared to light therapy alone . This persisted after adjustment for ongoing treatment with light therapy, antidepressants and psychotherapy. A more robust randomised control trial comparing CBT and light therapy is underway.

Herbal treatments

St John's wort has been found to be effective in the treatment of mild-to-moderate depression. There is some evidence that it is at least as effective as light therapy in the treatment of SAD[20].

Experimental treatments

Use of blue light instead of bright white light.

Use of a combination of light therapy and CBT.

Bupropion has been researched in a randomised controlled trial to review the possible prevention of SAD. Bupropion was administered by mouth from autumn to winter and was associated with a reduction in the rates of recurrence of depression. It may have a role to play in prevention of SAD .

Agomelatine is a new antidepressant which acts as a melatonin agonist and a 5HT2C antagonist. It may have potential benefits in the treatment os SAD[21].

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